The overall objectives of this proposal are to characterize canine lymphocyte subpopulations and to define their role in mediating and abrogating transfusion-induced sensitization and resistance to allogeneic marrow grafts. Specifically, we plan to define surface markers for dog lymphocytes by using fluorescence staining for surface immunoglobulins, rosette formation with Staph. protein A-coated sheep erythrocytes, xenogeneic antithymocyte sera and eventually monoclonal antibodies to specific surface antigens. Secondly, we will separate the various cell populations on Staph. protein A affinity columns, cotton and nylon wool columns and the fluorescence-activated cell sorter. Cells will then be studied in functional assays such as in vitro stimulation and blastogenesis marrow-lymphocyte co-cultures and an assay for plaque formation in gel. Thirdly, we will test in marrow grafting experiments which cells will induce sensitization, and which cells are responsible for mediating rejection. We also plan to define the cells which are able to overcome, in vivo, resistance to allogeneic marrow grafts, thus allowing engraftment across major histocompatibility barriers without inducing graft-versus-host disease.